环孢素治疗原发性肾病综合征的Meta分析

目的 评价环孢素治疗原发性肾病综合征(PNS)的疗效和安全性，比较在儿童和成人PNS间的异同。方法 检索Cochrane图书馆、PubMed、EMBASE、中国生物医学文献光盘数据库、中国期刊全文数据库和中国维普数据库，检索时间均从建库至2006年9月30日,由3名系统评价者进行资料提取和质量评价,对同质资料运用RevMan 4.2.8软件进行Meta分析。结果 共纳入15篇文献（n＝796）。根据随机方法、分配隐藏、盲法和随访情况描述评分，3篇为A级，10篇为B级，2篇为C级。按年龄、测量指标及干预措施进行亚组分析。Meta 分析结果示:①环孢素治疗组与安慰剂或空白对照组比较，儿童PNS研究:6个月时完全缓解率:OR = 12.64, 95％CI:1.46～109.48，6个月时总缓解率:OR=22.57,95％CI:4.56～111.76，要优于对照组；18个月时总缓解率:OR = 1.96, 95％CI:0.58～6.56，高血压发生率:OR=0.93,95％CI:0.11～7.59，终末期肾病发生率及病死率:OR = 0.63, 95％CI:0.12～3.47，与对照组差异无统计学意义；成人PNS研究:6个月时总缓解率（高质量文献组）:OR=11.48,95％CI:4.72～27.92，18个月时总缓解率:OR=2.71,95％CI:1.10～6.67， 优于安慰剂或空白对照组；高血压发生率高于安慰剂或空白对照组（OR=2.89,95％CI:1.23～6.80）；6个月时完全缓解率:OR = 1.92, 95％CI:0.78～4.70，6个月时总缓解率（低质量文献组）:OR=0.88,95％CI:0.34～2.30，终末期肾病发生率或病死率:OR=0.61,95％CI:0.28～1.33，与安慰剂或空白对照组差异无统计学意义。②环孢素联合糖皮质激素组与大剂量糖皮质激素（>1 mg·kg-1·d-1）组比较:儿童PNS研究:6个月时总缓解率优于大剂量糖皮质激素组:OR=1.79,95％CI:1.00～3.19；24个月时总缓解率与大剂量糖皮质激素组差异无统计学意义（OR=1.14,95％CI:0.56～2.32）。③环孢素治疗组与其他免疫抑制剂治疗组比较，儿童PNS研究:24个月时总缓解率:OR=0.10,95％CI:0.03～0.29，要差于对照组，6个月时完全缓解率:OR=126,95％CI:0.33～4.73，6个月时总缓解率:OR=1.57,95％CI:0.65～3.78，高血压发生率:OR=3.15,95％CI:0.12～82.16，与对照组差异无统计学意义。成人PNS研究:6个月时总缓解率:OR=7.77,95％CI:2.17～27.83，要优于对照组；6个月时完全缓解率:OR=1.01,95％CI:0.34～3.02，24个月时完全缓解率:OR=0.95,95％CI:0.35～2.57，终末期肾病发生率及病死率:OR=0.76,95％CI:0.26～2.24，与其他免疫抑制剂治疗组差异无统计学意义。环孢素与血管紧张素转换酶抑制剂比较，由于只有一项半随机对照试验纳入，因此其确切结果有待于进一步论证。结论 现有的证据显示:环孢素可以改善儿童和成人PNS的近期（6个月）疗效,不能改善其远期疗效（18或24个月）和终点疗效；总的趋势来看，环孢素治疗成人PNS疗效要好于儿童PNS，同时高血压发生率也要高于儿童PNS。

Meta-analysis of cyclosporine A treating primary nephritic syndrome in adults and children

Objective To assess and compare the efficacy and safety of cyclosporine A in the treatment of primary nephritic syndrome in adults and children. Methods The Cochrane library, Pubmed, EMBASE, CBMdis, CNKI and VIP were searched till September 30, 2006. Three reviewers assessed the quality of included studies, extracted data and processed meta-analysis of homogenous studies using RevMan 4.2.8. Results Fifteen studies involving 796 participants were included and graded in term of randomization, allocation concealment and blinding. Three studies were graded A, ten studies were graded B and the other two were graded C. Meta-analysis based on included studies showed: ① In children, the complete remission rate (6 months) (OR=12.64, 95％CI:1.46-109.48), and the complete or partial remission rate (6 months) (OR=22.57,95％CI:4.56-111.76) were higher in treatment group with cyclosporine than with placebo or without treatment; but there were no significant differences in the complete or partial remission rate (18 months) (OR=1.96,95％CI:0.58-6.56), the incidence of hypertension (OR=0.93,95％CI:0.11-7.59) and ESRD or mortality (OR=0.63,95％CI:0.12-3.47). In adults, the complete or partial remission rate in 6 months (OR=11.48,95％CI:4.72,27.92) and in 18 months (OR=2.71,95％CI:1.10-6.67), and the incidence of hypertension (OR=2.89,95％CI:1.23-6.80) were higher in treatment group with cyclosporine than control group in high quality studies, while there were no significant differences in the complete remission rate (6 months) (OR=1.92, 95％CI:0.78-4.70) and ESRD or mortality (OR=0.61,95％CI:0.28-1.33) in low quality studies. ② In children, the complete or partial remission rate in 6 months (OR=1.79,95％CI:1.00-3.19 ) was higher in the treatment group of cyclosporine A combined with prednisone than the group treated with high dose prednisone, but there was no significant difference in 24 months. ③ Compared with other immunodepressive drugs, in children the treatment group with cyclosporine A had lower complete or partial remission rate in 24 months (OR=0.10,95％CI:0.03-0.29), and no differences were found in the complete remission rate (6 months) (OR=1.26, 95％CI:0.33-4.73), the complete or partial remission rate（6 months）(OR=1.57,95％CI:0.65-3.78) and the incidence of hypertension (OR=3.15,95％CI:0.12-82.16) between two groups. In adults, the complete or partial remission rate was higher in the group treated with cyclosporine A than in that with other immunodepressive drugs, but no differences were found in the complete remission rate (6 months) (OR=1.01, 95％CI:0.34-3.02), the complete or partial remission rate (24 months) (OR=0.95,95％CI:0.35-2.57) and the ESRD or mortality (OR=0.76,95％CI:0.26-2.24) between two groups. ④ The evidence was not strong enough to judge whether the treatment with cyclosporin is superior to ACEI due to only one quasi-RCT was enrolled. Conclusions Available evidence showed cyclosporine A could improve short term efficacy in primary nephritic syndrome, but could not improve long term and endpoint efficacy. As a whole, there was a trend that the effect of cyclosporine A on nephritic syndrome for adults was superior to children. 